Skin Microdialysis-Based Estimation of Systemic Bioavailability Fraction

Systemic bioavailability is usually determined from plasma data. However, when plasma is difficult to access, as in young children, alternative methods would be particularly beneficial. The present study investigates the possibility of calculating systemic bioavailability fraction (F) from skin conc...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2012-01, Vol.101 (1), p.405-413
Main Authors: Juluru, Ravi, Shukla, Chinmay, Yin, Hongjun, Stagni, Grazia
Format: Article
Language:English
Subjects:
Administration, Oral
Amoxicillin - blood
Amoxicillin - pharmacokinetics
Animals
Area Under Curve
bioavailability
Biological and medical sciences
Biological Availability
Cross-Over Studies
dose-proportionality
Female
General pharmacology
Infusions, Intravenous
Ketoprofen - blood
Ketoprofen - pharmacokinetics
Medical sciences
microdialysis
Microdialysis - methods
oral absorption
Pharmaceutical technology. Pharmaceutical industry
pharmacokinetics
Pharmacology. Drug treatments
Rabbits
Skin - chemistry
Skin - metabolism
tissue partition
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Summary:Systemic bioavailability is usually determined from plasma data. However, when plasma is difficult to access, as in young children, alternative methods would be particularly beneficial. The present study investigates the possibility of calculating systemic bioavailability fraction (F) from skin concentrations measured by two microdialysis (MD) sampling methods: continuous microdialysis and intermittent microdialysis. When the drug concentration in skin is a linear and time-invariant function of plasma concentration, the area under the drug concentration curve in skin is directly proportional to the drug absorbed systemically. To verify this theory, we compared the F estimated from MD concentrations in the skin with that obtained from the plasma data in the same experiment. Two model drugs were selected for the study: amoxicillin and ketoprofen. Drugs were administered to rabbits as intravenous infusion or oral suspension according to a randomized crossover design. F estimated by either MD method was not significantly different from that obtained from the plasma for both drugs tested. However, the skin data exhibited a larger variability. These results confirm that skin MD could be an alternative way to obtain data for the calculation of systemic fraction of drug absorbed. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.22762